Glaring knowledge gaps in medical rehabilitation across the translational research spectrum demand rigorous, interdisciplinary clinical trials of th highest quality. We define these key gaps in three, equally important domains: (i) the fundamental underpinnings of both disease pathobiology and rehabilitation efficacy; (ii) optimal intervention strategies - in a disease-specific and population-specific manner - that maximize function and life quality; (iii) mechanisms to achieve the ultimate translation to clinical practic and user engagement. With particular emphasis on chronic conditions such as stroke, brain or spinal cord injury, orthopedic and joint conditions, and developmental and degenerative disorders leading to disability, the overarching purpose of the proposed P2C National Resource Center for High-Impact Clinical Trials in Medical Rehabilitation is to catalyze high-impact, interdisciplinary clinical trials nationally that will: (i) reveal fundamental underpinnings; (ii) efine optimal intervention strategies; and (iii) streamline translation to clinical and community-based application. The University of Alabama at Birmingham (UAB) is a leading-edge academic health center ideally positioned to achieve this stated purpose - with its unique depth and breadth of resources and collaborative expertise - complemented by a long-standing and extensive national network of partners to both support trials development and promote the Center's resources. The Center is carefully designed with an integrated research infrastructure - coordinating resources locally and nationally - that will significantly advance the field by encouraging medical rehabilitation researchers to take full advantage of specialized expertise and experience, an extensive menu of core resources and interdisciplinary research centers, and comprehensive study design and support services often not available through their local institutions or other organizations. This unique infrastructure will enable us to achieve the Center's purpose via the following specific aims: Aim 1. To advance the research of medical rehabilitation investigators nationally, we will provide effective consultative and/or educational services and collaborative arrangements that will facilitate all aspects of clinical trial design ad conduct, and competitive funding will be awarded nationally for innovative pilot projects needed to shape large-scale, definitive clinical trials (e.g., dosing trials, adaptive, delayed start, withdrawal and futility trials, and trials evaluating the interactions of complex mixtures of treatment modalities, etc.). Aim 2. To encourage medical rehabilitation researchers to take full advantage of the national resource Center's unique resources and expertise by effectively promoting and disseminating all of the Center's programs. Aim 3. To develop, validate, and provide state-of-the-art techniques and tools that will strengthen high-impact clinical trials nationally by enabling medical rehabilitation researchers to conduct more rigorous trials yielding higher quality data with potentially greater influence on clinical practice and health care deliver.